title: Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a gastric adenocarcinoma cell line (PG100).
abstract: There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions.
authors.affiliation: Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: J M C
authors.initials: JM
authors.lastname: Sousa
authors.forename: L A
authors.initials: LA
authors.lastname: Matos
authors.forename: D F A
authors.initials: DF
authors.lastname: Alcântara
authors.forename: H F
authors.initials: HF
authors.lastname: Ribeiro
authors.forename: L S
authors.initials: LS
authors.lastname: Santos
authors.forename: M N
authors.initials: MN
authors.lastname: Oliveira
authors.forename: L C
authors.initials: LC
authors.lastname: Brito-Junior
authors.forename: A S
authors.initials: AS
authors.lastname: Khayat
authors.forename: A C
authors.initials: AC
authors.lastname: Guimarães
authors.forename: L A
authors.initials: LA
authors.lastname: Cunha
authors.forename: R R
authors.initials: RR
authors.lastname: Burbano
authors.forename: M O
authors.initials: MO
authors.lastname: Bahia
mesh_terms: D000230:Adenocarcinoma; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001203:Ascomycota / Q000737:chemistry; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D008297:Male; D015162:Micronucleus Tests; D010647:Phenyl Ethers / Q000494:pharmacology*; D013274:Stomach Neoplasms
chemical_list: D000970:Antineoplastic Agents; D006843:Hydrocarbons, Chlorinated; D010647:Phenyl Ethers; C588350:pestheic acid; D004317:Doxorubicin